Werner & Ingbar's The Thyroid: A Fundamental and Clinical Text

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Contents
Section I: The Normal Thyroid
A. History, Development, Anatomy
Chapter 1: The heritage of the thyroid: A brief history
GOITER, CRETINISM, AND THE THYROID GLAND
GOITER AND IODINE
THYROTOXICOSIS
HYPOTHYROIDISM AND THE RECOGNITION OF THYROID FUNCTION
THERAPY OF HYPOTHYROIDISM
DISCOVERY OF THE ACTIVE PRINCIPLE AND THERAPY OF HYPOTHYROIDISM
SCREENING AND THERAPY OF CONGENITAL HYPOTHYROIDISM
DISCOVERY OF CURRENT CONCEPTS OF THYROID HORMONE SYNTHESIS, TRANSPORT, AND ACTION
AUTOIMMUNE ETIOLOGY OF GRAVES DISEASE AND HASHIMOTO THYROIDITIS
THYROID CANCER
OUTLOOK
REFERENCES
Chapter 2: Development and anatomy of the hypothalamic–pituitary–thyroid axis
THE HYPOTHALAMIC–PITUITARY AXIS
SIGNALING AND TRANSCRIPTIONAL MECHANISMS INVOLVED IN HYPOTHALAMUS ORGANOGENESIS
SIGNALING AND TRANSCRIPTIONAL MECHANISMS INVOLVED IN PITUITARY ORGANOGENESIS
THE THYROID GLAND
THYROID BUD FORMATION
THYROID MIGRATION
THYROID FOLLICULOGENESIS
DIFFERENTIATED THYROID FOLLICULAR CELLS
HISTOLOGY AND STRUCTURE
THYROID TRANSCRIPTION FACTORS
OTHER TRANSCRIPTION FACTORS INVOLVED IN THYROID DEVELOPMENT
IN VITRO GENERATION OF THYROID CELLS FROM PLURIPOTENT STEM CELLS
MODELING THYROID BY TRANSCRIPTION FACTORS OVEREXPRESSION
MODELING THYROID BY CHEMICAL PATHWAYS MANIPULATIONS
CONCLUSIONS
ACKNOWLEDGMENTS
REFERENCES
B. Thyroid Hormone Synthesis and Secretion
Chapter 3: Thyroid hormone synthesis: Thyroid iodide transport
IDENTIFICATION BY FUNCTIONAL EXPRESSION OF THE CDNA ENCODING RAT NIS
THE NIS MOLECULE
ISOLATION OF THE CDNA ENCODING HUMAN NIS (hNIS) AND ELUCIDATION OF THE GENOMIC ORGANIZATION OF hNIS
NIS IN EXTRATHYROIDAL TISSUES
NIS MECHANISM AND STOICHIOMETRY
SUBSTRATE SPECIFICITY OF NIS
NIS TRANSPORTS THE ENVIRONMENTAL POLLUTANT ClO4− WITH A 1 Na+:1 ClO4− STOICHIOMETRY
IODIDE TRANSPORT DEFECT, A CONGENITAL CONDITION CAUSED BY MUTATIONS IN THE NIS (SLC5A5) GENE
NIS KO MICE, A USEFUL MODEL FOR STUDYING MULTIPLE RAMIFICATIONS OF HYPOTHYROIDISM
REGULATION OF NIS TRANSCRIPTION
REGULATION OF NIS IN THE THYROID BY TSH
REGULATION OF NIS BY I−
REGULATION OF NIS BY A K+ CHANNEL
NIS IN THYROID CANCER
I− EFFLUX
NIS IN BREAST CANCER
IMPACT OF NIS ON PUBLIC HEALTH
NIS GENE TRANSFER
CONCLUDING REMARKS AND AVENUES FOR FUTURE INVESTIGATION
REFERENCES
Chapter 4: Thyroid hormone synthesis
IODIDE UPTAKE INTO THE THYROID
THE GENE AND PROTEIN STRUCTURE OF THE SODIUM/IODIDE SYMPORTER
FUNCTIONAL CHARACTERIZATION OF THE SODIUM/IODIDE SYMPORTER
REGULATION OF IODIDE UPTAKE AND SODIUM/IODIDE SYMPORTER FUNCTION AND EXPRESSION
MUTATIONS IN THE SODIUM/IODIDE SYMPORTER GENE
IODIDE EFFLUX FROM THE THYROID
PENDRED SYNDROME AND PENDRIN (PDS/SLC26A4)
PROTEIN STRUCTURE OF PENDRIN
EXPRESSION AND REGULATION OF PENDRIN
FUNCTIONAL CHARACTERIZATION OF PENDRIN
GOITER AND THYROID DYSFUNCTION IN PENDRED SYNDROME
ANOCTAMIN
SLC26A7
THYROGLOBULIN
STRUCTURE OF THE THYROGLOBULIN GENE AND PROTEIN
MUTATIONS IN THE THYROGLOBULIN GENE
THYROID PEROXIDASE
THE GENE AND PROTEIN STRUCTURE OF THYROID PEROXIDASE
FUNCTIONAL CHARACTERIZATION OF THYROID PEROXIDASE
EXPRESSION AND REGULATION OF THYROID PEROXIDASE
MUTATIONS IN THYROID PEROXIDASE
THE HYDROGEN PEROXIDE–GENERATING SYSTEM
CLONING OF THE DUAL OXIDASE AND THE DUAL OXIDASE MATURATION FACTOR GENES
THE PROTEIN STRUCTURE OF DUAL OXIDASES AND THE DUAL OXIDASE MATURATION FACTORS
EXPRESSION AND REGULATION OF DUAL OXIDASES AND THE DUAL OXIDASE MATURATION FACTORS
MECHANISM OF HYDROGEN PEROXIDE GENERATION
REGULATION OF HYDROGEN PEROXIDE ACTIVITY
GENETIC DEFECTS IN HYDROGEN PEROXIDE GENERATION
IODINATION AND THYROID HORMONE SYNTHESIS
OXIDATION OF THYROID PEROXIDASE TO COMPOUND I AND COMPOUND II
OXIDATION OF IODIDE
IODINATION AND COUPLING OF TYROSYL RESIDUES
INHIBITION OF THYROID PEROXIDASE BY THIONAMIDE DRUGS
CELLULAR UPTAKE AND PROTEOLYSIS OF THYROGLOBULIN
SECRETION OF THYROID HORMONES
DEHALOGENATION OF MONOIODOTYROSINE AND DIIODOTYROSINE
IODOTYROSINE (IYD/DEHAL1) DEIODINASE GENE AND PROTEIN
DEHALOGENASE DEFICIENCY
REFERENCES
C. Peripheral Thyroid Hormone Binding and Metabolism
Chapter 5: Thyroid hormone transport proteins
EVOLUTIONARY CONSIDERATIONS
FUNCTIONS OF THBPs
CLINICAL CONSIDERATIONS
THYROID-BINDING GLOBULIN
STRUCTURE AND FUNCTION
PHYSIOLOGIC REGULATION OF TBG IN HUMANS
PATHOLOGY
HUMAN SERPINA7 GENE SEQUENCE VARIANTS AFFECTING TBG CONCENTRATION OR FUNCTION
TRANSTHYRETIN
STRUCTURE AND FUNCTION
PHYSIOLOGIC REGULATION OF TTR IN HUMANS
PATHOLOGY
HUMAN TTR GENE SEQUENCE VARIANTS AFFECTING TTR CONCENTRATION OR FUNCTION
DYSTRANSTHYRETINEMIC HYPERTHYROXINEMIA
ALBUMIN
STRUCTURE AND FUNCTION
PATHOPHYSIOLOGY
HUMAN ALB GENE VARIANTS AFFECTING ALB CONCENTRATION OR FUNCTION
p.Arg242His
OTHER SEQUENCE VARIANTS AT Arg242
p.Arg246Ile
T3 VARIANTS OF FDH
MINOR CARRIERS
CLINICAL IMPLICATIONS OF THBPs
REFERENCES
Chapter 6: Intracellular pathways of iodothyronine metabolism/implications of deiodination for thyroid hormone action
STRUCTURE OF THE DEIODINASES
TOPOLOGY AND SUBCELLULAR LOCALIZATION
STRUCTURE–FUNCTION RELATIONSHIPS OF DEIODINASES AND MECHANISM OF DEIODINATION
SPECIFIC PROPERTIES OF THE DEIODINASES
TYPE 1 DEIODINASE
TYPE 2 DEIODINASE
TYPE 3 DEIODINASE
NONDEIODINATIVE METABOLISM OF IODOTHYRONINES
PHYSIOLOGIC ROLES OF THE SELENODEIODINASES
DEIODINASES AND THE REGULATION OF T3 PRODUCTION
ADAPTATION TO HYPOTHYROIDISM
INTRACELLULAR TRIIODOTHYRONINE HOMEOSTASIS
DEIODINASES AND REGULATION OF THYROTROPIN SECRETION
DEIODINASES AND THE BIOLOGIC EFFECTS OF THYROID HORMONE
DEIODINASES AND THE CENTRAL NERVOUS SYSTEM
DEIODINASES AND THE SKELETON
DEIODINASES AND METABOLISM
DEVELOPMENTAL ROLES OF THE DEIODINASES
MATERNAL–FETAL PHYSIOLOGY
TRIIODOTHYRONINE MODULATION OF PLACENTAL THYROID HORMONE TRANSFER
D3 EXPRESSION AND THE REQUIREMENT FOR THYROXINE IN NORMAL PREGNANCY
THE DEIODINASES IN HUMAN PATHOPHYSIOLOGY
NONTHYROIDAL ILLNESS
CONSUMPTIVE HYPOTHYROIDISM
DEIODINASES IN CANCER
HYPERTHYROIDISM AND OVEREXPRESSION OF DEIODINASES
DEIODINASES IN THE ISCHEMIC HEART
DEIODINASES IN LUNG INJURY
CONCLUSION
ACKNOWLEDGMENT
REFERENCES
D. Thyroid Hormone Action
Chapter 7: Intracellular actions by thyroid hormones
THYROID HORMONE TRANSPORT AND METABOLISM
TR-DEPENDENT SIGNALING OF TH WITH DIRECT BINDING TO DNA (TYPE 1)
THYROID HORMONE RESPONSE ELEMENTS
TRANSCRIPTIONAL REGULATION BY TRs
THYROID HORMONE RECEPTOR–INTERACTING COREPRESSORS/BASAL REPRESSION
THYROID HORMONE RECEPTOR–INTERACTING COACTIVATORS/TRANSCRIPTIONAL ACTIVATION
NEGATIVE REGULATION BY TRs
POSTTRANSLATIONAL MODIFICATION OF TR
RESISTANCE TO TH
THYROID HORMONE RECEPTOR ISOFORM KNOCKOUT AND KNOCKIN MICE
TRANSCRIPTIONAL CASCADES
TR-DEPENDENT SIGNALING OF TH WITH INDIRECT BINDING TO DNA (TYPE 2)
TR-DEPENDENT SIGNALING OF TH WITHOUT DNA BINDING (TYPE 3)
TR-INDEPENDENT TH SIGNALING (TYPE IV)
TH ANALOGS, DISRUPTORS, AND METABOLITES
SUMMARY
REFERENCES
Chapter 8: Thyroid hormone structure–function relationships
THYROID HORMONE STRUCTURE, METABOLISM, AND ACTIVITY
TR ACTIVATION BY NATURAL AND SYNTHETIC AGONISTS
DEVELOPMENT OF SELECTIVE TR SUBTYPE AGONISTS
STRUCTURE–FUNCTION RELATIONSHIPS AT TR MUTANTS—THE ISSUE OF TH RESISTANCE
TR ANTAGONISM
THYROID HORMONE INTERACTIONS WITH ALTERNATE RECEPTORS AND BINDING PROTEINS
THYRONAMINES AND ANALOGS
CONCLUSION
REFERENCES
E. Factors That Control Thyroid Function
Chapter 9: Chemistry and biosynthesis of thyrotropin
CHEMISTRY
GENES ENCODING THE SUBUNITS OF THYROTROPIN
CHROMOSOME LOCALIZATION
STRUCTURE OF THE COMMON α-SUBUNIT GENE
STRUCTURE OF THE THYROTROPIN-β–SUBUNIT GENE
CENTRAL HYPOTHYROIDISM DUE TO THYROTROPIN-β–SUBUNIT GENE ABNORMALITIES
PRETRANSLATIONAL REGULATION OF THYROTROPIN BIOSYNTHESIS
NEGATIVE REGULATORS
POSITIVE REGULATORS
SUMMARY OF PRETRANSLATION REGULATION OF THE HUMAN COMMON α- AND TSH-β–SUBUNIT GENE EXPRESSION
POSTTRANSLATIONAL PROCESSING OF THYROTROPIN
IN VITRO TRANSLATION OF THYROTROPIN-β–SUBUNIT AND α-SUBUNIT MESSENGER RNA
BIOSYNTHESIS OF THYROTROPIN IN INTACT CELLS
PROCESSING OF HIGH-MANNOSE PRECURSOR OLIGOSACCHARIDES
TERMINAL SULFATION AND SIALYLATION OF COMPLEX OLIGOSACCHARIDES
DEVELOPMENTAL AND ENDOCRINE REGULATION OF THYROTROPIN GLYCOSYLATION
BIOACTIVITY AND METABOLIC CLEARANCE OF THYROTROPIN
THREE-DIMENSIONAL CONFORMATION OF THYROTROPIN
RECOMBINANT HUMAN THYROTROPIN
REFERENCES
Chapter 10: The thyrotropin receptor
THE STRUCTURE OF THE THYROTROPIN RECEPTOR
THE THYROTROPIN RECEPTOR GENE
RECOGNITION OF THE RECEPTOR BY THYROTROPIN
PROPOSED MECHANISM OF ACTIVATION OF THE RECEPTOR BY TSH
ACTIVATION BY THYROSTIMULIN
ACTIVATION BY CHORIONIC GONADOTROPIN
ACTIVATION BY THYROTROPIN-RECEPTOR ANTIBODIES
ACTIVATION BY LOW–MOLECULAR-WEIGHT DRUG-LIKE CHEMICALS
DOWNREGULATION OF THE THYROTROPIN RECEPTOR
REFERENCES
Chapter 11: Aging and the thyroid
CHANGES IN THYROID ANATOMY WITH AGE
PHYSIOLOGIC CHANGES IN THYROID FUNCTION WITH AGE
CHALLENGES IN THE DIAGNOSIS AND MANAGEMENT OF THYROID DYSFUNCTION WITH AGE
CHALLENGES IN THE DIAGNOSIS AND MANAGEMENT OF NODULAR DISEASE AND THYROID CANCER
SUMMARY
REFERENCES
Chapter 12: Effects of drugs on TSH secretion, thyroid hormones’ absorption, synthesis, metabolism, and action
INTRODUCTION
DRUGS THAT ALTER SERUM TSH LEVELS (FIG. 12-1, PANEL 1)
DOPAMINE/DOPAMINE AGONISTS AND ANTAGONISTS
SOMATOSTATIN AND SOMATOSTATIN ANALOGS
REXINOIDS
OTHER DRUGS THAT SUPPRESS TSH SECRETION
DRUGS THAT REDUCE THYROID HORMONE ABSORPTION
BILE ACID SEQUESTRANTS
FERROUS SULFATE
SUCRALFATE AND ALUMINUM-CONTAINING ANTACIDS
CALCIUM CARBONATE AND PHOSPHATE BINDERS
OTHER MEDICATIONS THAT MAY REDUCE T4 INTESTINAL ABSORPTION
DRUGS THAT REDUCE SYNTHESIS AND SECRETION OF THYROID HORMONES (FIG. 12-1, PANEL 2)
THIONAMIDES (ANTITHYROID DRUGS)
IONIC INHIBITORS (PERCHLORATE, THIOCYANATE; SEE Chapter 13 ON THYROID DISRUPTORS)
LITHIUM
DRUGS THAT ALTER THE METABOLISM OF THYROID HORMONES (FIGS. 12-1, PANEL 3 AND 12-2)
DRUGS THAT INDUCE CYP3a (PHENYTOIN, CARBAMAZEPINE, PHENOBARBITAL, RIFAMPIN, RITONAVIR, SERTRALINE)
DRUGS THAT INHIBIT THE DEIODINATION OF T4 AND T3
PROPYLTHIOURACIL
PROPRANOLOL AND NADOLOL
DRUGS THAT ALTER THE TRANSPORT OR ACTION OF THYROID HORMONES (FIG. 12-1, PANEL 3)
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (SALICYLATES, SALSALATE, FENCLOFENAC)
FUROSEMIDE
HEPARIN AND FATTY ACIDS
ESTROGEN AND SELECTIVE ESTROGEN MODULATORS (SERM) (TAMOXIFEN, RALOXIFENE)
ANDROGENS
OTHER DRUGS ALTERING TBG LEVELS
DRUGS ACTING AT MULTIPLE SITES TO ALTER THYROID HORMONE HOMEOSTASIS
IODINATED RADIOGRAPHIC CONTRAST AGENTS
PHENYTOIN
AMIODARONE
GLUCOCORTICOIDS
CYTOKINES (INTERFERON, INTERLEUKIN, AND TUMOR NECROSIS FACTOR)
TYROSINE KINASE INHIBITORS
DRUGS ALTERING THYROID FUNCTION THROUGH ALTERATIONS IN IMMUNITY
IMMUNE RECONSTITUTION SYNDROME
ANTI-CD52 ANTIBODY ALEMTUZUMAB
CHECKPOINT INHIBITORS
REFERENCES
Chapter 13: Thyroid disruptors
INTRODUCTION
SUBSTANCES THAT INHIBIT THYROIDAL IODINE UPTAKE
PERCHLORATE
THIOCYANATE
NITRATE
COMPOUNDS WITH DIRECT ACTIONS ON THE THYROID HORMONE RECEPTOR
POLYCHLORINATED BIPHENYLS
POLYBROMINATED DIPHENYL ETHERS
BISPHENOL-A AND PHTHALATES
TRICLOSAN
COMPOUNDS THAT DISPLACE T4 FROM SERUM THYROID BINDING PROTEINS
PCBs AND PBDEs
COMPOUNDS THAT INHIBIT THYROPEROXIDASE ACTIVITY
ISOFLAVONES
COMPOUNDS THAT DECREASE T4 HALF-LIFE BY ACTIVATING HEPATIC ENZYMES
ORGANOCHLORINE PESTICIDES
DIOXINS AND FURANS
COMPOUNDS THAT INHIBIT DEIODINASE ACTIVITY
OTHER EXPOSURES
STYRENES
PERFLUORINATED AND GEN X COMPOUNDS
ORGANOPHOSPHATE PESTICIDES
SUNSCREENS
LEAD
SUMMARY
REFERENCES
Chapter 14: Nonthyroidal illness syndrome
INTRODUCTION
DESCRIPTION OF NTIS
CHANGES IN SERUM THYROID HORMONE AND THYROTROPIN CONCENTRATIONS
CHANGES IN THYROID HORMONE KINETICS
CHANGES IN THE HYPOTHALAMIC–PITUITARY–THYROID AXIS
CHANGES IN PERIPHERAL THYROID HORMONE METABOLISM
PATHOGENESIS OF NTIS
PATHOGENESIS OF CHANGES IN THE HYPOTHALAMIC–PITUITARY–THYROID AXIS
CHANGES IN HPT AXIS DURING FASTING
CHANGES IN HPT AXIS DURING ILLNESS
PATHOGENESIS OF CHANGES IN PERIPHERAL THYROID HORMONE METABOLISM
CHANGES IN SERUM IODOTHYRONINE–BINDING PROTEINS
CHANGES IN IODOTHYRONINE TRANSPORT INTO TISSUES
CHANGES IN IODOTHYRONINE DEIODINASES
CHANGES IN IODOTHYRONINE NUCLEAR RECEPTORS
CLINICAL RELEVANCE OF NTIS
PROGNOSTIC IMPORTANCE OF NTIS
DIAGNOSIS OF THYROID DISEASE IN NTIS
TREATMENT OF PATIENTS WITH NTIS
SPECIFIC TYPES OF NTIS
CHRONIC RENAL FAILURE
LIVER DISEASE
HUMAN IMMUNODEFICIENCY VIRUS INFECTION
PSYCHIATRIC DISEASE
CONCLUSION
REFERENCES
Chapter 15: Iodine deficiency and excess, endemic cretinism
INTRODUCTION
THE ECOLOGY OF IODINE
DIETARY SOURCES, ABSORPTION, AND METABOLISM OF IODINE
GOITROGENS
IODINE REQUIREMENTS
ADULTHOOD
PREGNANCY AND LACTATION
INFANCY AND CHILDHOOD
ASSESSMENT OF IODINE DEFICIENCY
URINARY IODINE CONCENTRATION
BREAST MILK IODINE CONCENTRATION
THYROID SIZE
THYROID-STIMULATING HORMONE AND THYROID HORMONES
THYROGLOBULIN
EFFECTS OF IODINE DEFICIENCY
THYROIDAL ADAPTATION TO IODINE DEFICIENCY
EFFECTS OF HYPOTHYROIDISM DUE TO IODINE DEFICIENCY ON THE DEVELOPING BRAIN
CRETINISM
THE BENEFITS OF CORRECTION OF IODINE DEFICIENCY
IODINE INTERVENTIONS IN SEVERELY DEFICIENT PREGNANT WOMEN
IODINE INTERVENTIONS IN MILD TO MODERATELY DEFICIENT PREGNANT WOMEN
INFANCY
CHILDHOOD
ADULTHOOD
THYROID CANCER
EPIDEMIOLOGY
TREATMENT AND PREVENTION
SALT FORTIFICATION WITH IODINE
IODINE SUPPLEMENTATION
EFFECTS OF EXCESS IODIDE
PHYSIOLOGIC RESPONSE TO EXCESS IODIDE
TOLERABLE UPPER LIMITS FOR IODINE INTAKE
MONITORING OF IODINE EXCESS IN POPULATIONS
SOURCES OF EXCESS IODIDE
IODINE-INDUCED HYPOTHYROIDISM OR GOITER IN THE ABSENCE OF APPARENT UNDERLYING THYROID DISEASE
IODINE AND THYROIDITIS
IODINE-INDUCED THYROTOXICOSIS
AMIODARONE-INDUCED THYROID DISEASE (SEE Chapter 11)
REFERENCES
Section II: Assessment of Thyroid Structure and Function
Chapter 16: Physical examination of the thyroid gland
HISTORY
PHYSICAL EXAMINATION
INSPECTION
PALPATION
FACING THE PATIENT
STANDING BEHIND THE PATIENT
AUSCULTATION
PALPATING LOBES AND EVALUATING THYROID SIZE
THYROID NODULES
HEMIAGENESIS
CONSISTENCY
PAIN/TENDERNESS
LYMPHADENOPATHY
DISTINGUISHING BENIGN FROM MALIGNANT DISEASE
REFERENCES
Chapter 17: Laboratory measurement of thyroid-related hormones, proteins, and autoantibodies in serum
INTRODUCTION
NOMENCLATURE FOR SENSITIVITY AND ASSESSMENT OF ASSAYS
FUNCTIONAL VERSUS ANALYTICAL SENSITIVITY OF ASSAYS
THYROID-STIMULATING HORMONE
METHODS FOR SERUM TSH MEASUREMENTS
REQUIREMENTS FOR SERUM TSH MEASUREMENTS
TSH ISOFORMS
INDICATIONS FOR TRH TESTING
TSH REFERENCE INTERVALS
THE CLINICAL UTILITY OF TSH MEASUREMENT
TSH AND THYROID FUNCTION ASSESSMENT IN PREGNANCY (SEE Chapter 66)
HOSPITALIZED PATIENTS
THYROID HORMONE MEASUREMENTS
SERUM TOTAL THYROID HORMONE (TT4 AND TT3) ASSAY METHODOLOGY
CLINICAL UTILITY OF TT4 AND TT3 MEASUREMENTS
TT4 AND TT3 REFERENCE INTERVALS
SERUM FREE THYROID HORMONE TESTS (FT4 AND FT3)
DIRECT FT4 AND FT3 METHODS
INDIRECT FT4 AND FT3 ESTIMATE TESTS
SERUM-FREE THYROXINE AND FREE TRIIODOTHYRONINE INDEXES
THYROID HORMONE–BINDING PROTEINS
FAMILIAL DYSALBUMINEMIC AND TRANSTHYRETIN-ASSOCIATED HYPERTHYROXINEMIAS
SERUM THYROGLOBULIN (Tg)
REQUIREMENTS FOR SERUM Tg METHODS
FACTORS THAT INFLUENCE CIRCULATING Tg CONCENTRATIONS
ANALYTICAL AND TECHNICAL CONSIDERATION
THYROID-SPECIFIC AUTOANTIBODIES
ANTI–TSH RECEPTOR AUTOANTIBODIES
ANTITHYROID PEROXIDASE AUTOANTIBODIES
ANTITHYROGLOBULIN AUTOANTIBODIES
INTERFERENCES WITH THYROID TEST OUTCOMES
INTERFERENCES WITH THYROID MEASUREMENT METHODOLOGIES
ASSAY INTERFERENCES
AUTOMATION OF THYROID TESTS
REFERENCES
Chapter 18: Nonisotopic thyroid imaging
INTRODUCTION
PLAIN RADIOGRAPHY
ULTRASONOGRAPHY
BASIC PHYSICS AND TECHNICAL PRINCIPLES (1)
CONDUCTING THE EXAMINATION
CLINICAL APPLICATIONS
DEVELOPMENTAL ABNORMALITIES
THE NORMAL THYROID GLAND
GOITER
DIFFUSE NONNEOPLASTIC THYROID DISEASES
NODULES AND MULTINODULAR GOITER
INTERVENTIONAL PROCEDURES
COMPUTED TOMOGRAPHY
BASIC PHYSICS PRINCIPLES (22)
THE NORMAL THYROID GLAND
DIFFUSE THYROID DISEASE
INCIDENTALOMAS
CT IN LARGE BENIGN GOITERS
ECTOPIC THYROID TISSUE
CT AND PREOPERATIVE PLANNING OF THYROID CARCINOMAS, LYMPHOMAS, AND METASTASIS
CT AND FOLLOW-UP OF THYROID CARCINOMAS
MAGNETIC RESONANCE IMAGING
BASIC PHYSICS PRINCIPLES (41)
NORMAL THYROID TISSUE
DIFFUSE THYROID DISEASE
THYROID INCIDENTALOMAS AND NODULE CHARACTERIZATION
PREOPERATIVE PLANNING OF THYROID CARCINOMAS: ASSESSING INVASION (48)
FOLLOW-UP OF THYROID CARCINOMAS
CONCLUSION
REFERENCES
Chapter 19: Thyroid radionuclide uptake and imaging studies
INTRODUCTION
RADIOPHARMACEUTICALS
MODALITIES
RADIOIODINE
UPTAKE STUDIES
PLANAR IMAGING: HYPERTHYROIDISM
PLANAR IMAGING: THYROID CANCER
TOMOGRAPHY
DOSIMETRY
FDG PET/CT IN THYROID CANCER
FDG PET/CT IN INCIDENTAL THYROID DISEASE
IMAGING OF MEDULLARY THYROID CANCER
CONCLUSIONS
REFERENCES
Chapter 20: Cytopathology of the thyroid gland
INTRODUCTION
SPECIMEN PREPARATIONS
THYROID FNA CLASSIFICATION
NONDIAGNOSTIC OR UNSATISFACTORY (CATEGORY I)
BENIGN (CATEGORY II)
ATYPIA OF UNDETERMINED SIGNIFICANCE/FOLLICULAR LESION OF UNDETERMINED SIGNIFICANCE (AUS/FLUS) (CATEGORY III)
FOLLICULAR OR ONCOCYTIC (HüRTHLE-CELL) NEOPLASM OR SUSPICIOUS FOR FOLLICULAR OR ONCOCYTIC (HüRTHLE-CELL) NEOPLASM (CATEGORY IV)
SUSPICIOUS FOR MALIGNANCY (CATEGORY V)
MALIGNANT (CATEGORY VI)
CORE NEEDLE BIOPSY
KEY CYTOMORPHOLOGIC FEATURES OF THYROID FINE-NEEDLE ASPIRATION DIAGNOSES
DIFFUSE TOXIC GOITER
CHRONIC LYMPHOCYTIC THYROIDITIS (11,15)
ATYPIA OF UNDETERMINED SIGNIFICANCE/FOLLICULAR LESION OF UNDETERMINED SIGNIFICANCE (AUS/FLUS)
SUSPICIOUS FOR FOLLICULAR NEOPLASM/FOLLICULAR NEOPLASM (INCLUDING TUMORS WITH ONCOCYTIC FEATURES)
MALIGNANT LESIONS
PAPILLARY THYROID CARCINOMA AND ITS VARIANTS
MEDULLARY THYROID CARCINOMA
POORLY DIFFERENTIATED CARCINOMA
ANAPLASTIC CARCINOMA
ROLE OF ANCILLARY STUDIES IN THE DIAGNOSIS OF THYROID TUMORS IN CYTOLOGIC SPECIMENS’ IMMUNOHISTOCHEMISTRY
REFERENCES
Chapter 21: Histopathology of the thyroid gland
NORMAL THYROID
PATHOLOGIC DIAGNOSIS OF THYROID LESIONS
DEVELOPMENTAL VARIATIONS
GOITER
GRAVES DISEASE/DIFFUSE TOXIC GOITER
DYSHORMONOGENETIC GOITER
IATROGENIC AND RELATED HYPERPLASIAS
AUTOIMMUNE THYROIDITIS
SILENT THYROIDITIS
SPECIFIC INFECTIOUS THYROIDITIS
GRANULOMATOUS THYROIDITIS
PALPATION THYROIDITIS
AMIODARONE INJURY WITH THYROTOXICOSIS
RIEDEL THYROIDITIS (AKA RIEDEL STRUMA)
COMBINED RIEDEL STRUMA AND FIBROSING HASHIMOTO THYROIDITIS
MISCELLANEOUS DISORDERS
RADIATION EFFECTS
AMYLOIDOSIS
BLACK THYROID
NEOPLASMS
BENIGN NEOPLASMS
ADENOMAS AND ADENOMATOUS NODULES
MALIGNANT NEOPLASMS
PAPILLARY CARCINOMA
FOLLICULAR CARCINOMA
HÜRTHLE-CELL NEOPLASM/ONCOCYTIC FOLLICULAR NEOPLASM
PATHOLOGIC DIAGNOSIS OF PAPILLARY AND FOLLICULAR CARCINOMA OF THYROID: CONTROVERSIES
CLEAR CELL TUMORS
HIGH-GRADE THYROID CARCINOMA
POORLY DIFFERENTIATED THYROID CARCINOMA
ANAPLASTIC CARCINOMA
SQUAMOUS CELL CARCINOMA, MUCOEPIDERMOID CARCINOMA, AND INTRATHYROIDAL THYMOMA-LIKE NEOPLASMS
MEDULLARY THYROID CARCINOMA
CALCITONIN NEGATIVE NEUROENDOCRINE CARCINOMA OF THYROID
LYMPHOMA
SARCOMA
CARCINOMA IN ECTOPIC THYROID TISSUE
METASTATIC NEOPLASMS
REFERENCES
Section III: Thyroid Diseases: Thyrotoxicosis
A. Causes of Thyrotoxicosis
Chapter 22: Pathogenesis of Graves disease
INTRODUCTION
AUTOIMMUNITY
DEFINITION OF AN AUTOANTIGEN
THE NATURE OF T CELLS
ANTIBODY AND T-CELL INTERACTIONS WITH ANTIGEN
SECOND SIGNALS
CRITERIA FOR AN AUTOIMMUNE DISEASE
RESTRICTION VERSUS POLYCLONALITY
THYROID IMMUNOLOGY
INTRATHYROIDAL B CELLS
AUTOANTIBODIES TO THE HUMAN TSHR
BIOACTIVITY OF TSHR ANTIBODIES
PREVALENCE OF TSHR ANTIBODIES IN GRAVES DISEASE
IMMUNOLOGIC CHARACTERISTICS OF TSHR ANTIBODIES
TSHR FUNCTION IN GRAVES DISEASE
LESSONS FROM MONOCLONAL TSHR ANTIBODIES WITH STIMULATING ACTIVITY
OTHER THYROID ANTIBODIES IN GRAVES DISEASE
THE INTRATHYROIDAL LYMPHOCYTIC INFILTRATE
FUNCTIONAL ANALYSIS OF INTRATHYROIDAL T CELLS
T-CELL SELECTION
APOPTOSIS IN GRAVES DISEASE
THE INTRATHYROIDAL T-CELL RECEPTOR V GENE REPERTOIRE
REGULATORY EFFECTS OF T CELLS IN AUTOIMMUNE THYROID DISEASE
THE Th17 CELLS
IMMUNE MECHANISMS IN THE PATHOGENESIS OF GRAVES DISEASE
FAILURE OF IMMUNE CELL DELETION AND/OR SUPPRESSION
SPECIFICITY CROSSOVER (MOLECULAR MIMICRY)
BYSTANDER EFFECTS
EPIGENETIC CHANGES
THYROID CELL EXPRESSION OF HLA MOLECULES
ANIMAL MODELS OF GRAVES DISEASE
KNOWN RISK FACTORS FOR PRECIPITATING GRAVES DISEASE (TABLE 22-5)
SUSCEPTIBILITY GENES
INFECTION
THYROID AUTOANTIBODIES
THYROID TISSUE DAMAGE
STRESS
SEX STEROIDS
THE X CHROMOSOME
THE POSTPARTUM PERIOD
MATERNAL MICROCHIMERISM
IODINE
IRRADIATION
OVERVIEW OF THE ETIOLOGY OF GRAVES DISEASE
REFERENCES
Chapter 23: Thyrotropin-induced thyrotoxicosis
INTRODUCTION
EPIDEMIOLOGY
PATHOLOGIC AND PATHOGENIC ASPECTS
SIGNS AND SYMPTOMS
LABORATORY AND BIOCHEMICAL FEATURES
SERUM THYROTROPIN AND THYROID HORMONE LEVELS
PITUITARY GLYCOPROTEIN HORMONE α-SUBUNIT
PARAMETERS OF PERIPHERAL THYROID HORMONE ACTION
DIAGNOSTIC TESTING
IMAGING STUDIES AND LOCALIZATION
DIFFERENTIAL DIAGNOSIS
TREATMENT AND OUTCOME
CRITERIA OF CURE AND FOLLOW-UP
REFERENCES
Chapter 24: Toxic adenoma and toxic multinodular goiter
EPIDEMIOLOGY
CLINICAL ASPECTS OF THYROID AUTONOMY
DIAGNOSIS OF THYROID AUTONOMY
NATURAL HISTORY
MORPHOLOGY
ETIOLOGY
LESSONS FROM EPIDEMIOLOGIC STUDIES
FROM HYPERPLASTIC GROWTH TO NODULAR TRANSFORMATION
TRANSFORMATION TO HOT THYROID NODULES
TREATMENT OF AUTONOMOUS THYROID NODULES (SEE CHAPTER 32)
SURGERY
RADIOIODINE THERAPY
COST-EFFECTIVE MANAGEMENT OF THYROID AUTONOMY
FOLLOW-UP
ACKNOWLEDGMENT
REFERENCES
Chapter 25: Trophoblastic tumors
INTRODUCTION
HUMAN CHORIONIC GONADOTROPIN
GRADATIONS OF SEVERITY
CLINICAL FEATURES
DIAGNOSIS
HYPEREMESIS GRAVIDARUM
MUTANT THYROID-STIMULATING HORMONE RECEPTOR
THERAPY
REFERENCES
Chapter 26: Sporadic painless, painful subacute and acute infectious thyroiditis
INTRODUCTION
DESTRUCTION-INDUCED THYROIDITIS
PAINFUL THYROID
SPORADIC PAINLESS THYROIDITIS
ETIOLOGY
CLINICAL MANIFESTATIONS
LABORATORY FINDINGS
CYTOLOGY
IMAGING
PATHOLOGY
DIFFERENTIAL DIAGNOSIS
CLINICAL MANAGEMENT
SUBACUTE THYROIDITIS
ETIOLOGY
INFECTIOUS ASSOCIATION
AUTOIMMUNE ASSOCIATION
GENETIC ASSOCIATION
CLINICAL MANIFESTATIONS
LABORATORY FINDINGS
CYTOLOGY
IMAGING
PATHOLOGY
DIFFERENTIAL DIAGNOSIS
CLINICAL MANAGEMENT
ACUTE INFECTIOUS THYROIDITIS
ETIOLOGY
BACTERIAL INFECTIONS
FUNGAL INFECTIONS
MYCOBACTERIAL INFECTIONS
PARASITIC INFECTIONS
SYPHILITIC INFECTIONS
THYROIDAL INFECTIONS IN IMMUNOCOMPROMISED PATIENTS
CLINICAL MANIFESTATIONS
LABORATORY FINDINGS
CYTOLOGY
IMAGING STUDIES
CLINICAL MANAGEMENT
REFERENCES
Chapter 27: Thyrotoxicosis of extrathyroidal origin
INTRODUCTION
EXOGENOUS THYROID HORMONE
CAUSES
CLINICAL PRESENTATION AND DIAGNOSIS
TREATMENT
THYROTOXICOSIS DUE TO METASTATIC THYROID CARCINOMA
DEFINITION AND EPIDEMIOLOGY
CLINICAL PRESENTATION AND DIAGNOSIS
TREATMENT
STRUMA OVARII
DEFINITION AND EPIDEMIOLOGY
CLINICAL PRESENTATION AND DIAGNOSIS
TREATMENT
ACKNOWLEDGMENT
REFERENCES
B. Organ System Manifestations
Chapter 28: Overview of the clinical manifestations of thyrotoxicosis
INTRODUCTION
PREVALENCE OF CLINICAL FINDINGS
ORGAN SYSTEM–SPECIFIC MANIFESTATIONS
CENTRAL NERVOUS SYSTEM
BEHAVIORAL HEALTH MANIFESTATIONS
CARDIOVASCULAR MANIFESTATIONS
PULMONARY MANIFESTATIONS
GASTROINTESTINAL MANIFESTATIONS
RENAL MANIFESTATIONS
INTEGUMENTARY FINDINGS
MUSCULOSKELETAL MANIFESTATIONS
REPRODUCTIVE CHANGES
HEMATOLOGIC MANIFESTATIONS
MODULATING FACTORS
AGE
PREGNANCY
COMORBIDITY
ETIOLOGY OF THYROTOXICOSIS
CLINICAL ASSESSMENT
REFERENCES
Chapter 29: Ophthalmopathy
INTRODUCTION
EPIDEMIOLOGY AND NATURAL HISTORY
PATHOGENESIS
RISK FACTORS AND PREVENTION
CLINICAL PRESENTATION
DIAGNOSIS
TREATMENT OF HYPERTHYROIDISM IN PATIENTS WITH GO
MANAGEMENT OF GO
CONCLUSIONS
REFERENCES
Chapter 30: The cardiovascular system in thyrotoxicosis
THYROID HORMONE ACTION ON THE HEART AND VASCULAR SYSTEM
CLINICAL CONSEQUENCES OF THYROTOXICOSIS
CARDIOVASCULAR SYMPTOMS AND SIGNS IN THYROTOXICOSIS
ATRIAL FIBRILLATION
ELECTROCARDIOGRAPHIC CHANGES
HEART FAILURE
HYPERTENSION AND VASCULAR DYSFUNCTION
MAJOR ADVERSE CARDIOVASCULAR EVENTS
ROLE OF OTHER HORMONES IN THYROTOXICOSIS
SUBCLINICAL THYROTOXICOSIS
AMIODARONE AND IODINE CONTAINING CONTRAST AGENTS
REFERENCES
Chapter 31: Thyroid hormones in intermediary metabolism, thermogenesis, and obesity
THYROID HORMONE SIGNALING, TISSUE- AND TARGET GENE–SPECIFICITY IN RELATION TO INTERMEDIARY AND ENERGY METABOLISM
THYROID HORMONE ACTION ON INTERMEDIARY METABOLISM
CARBOHYDRATE METABOLISM
CLINICAL CORRELATES
PROTEIN METABOLISM
CLINICAL CORRELATES
LIPID METABOLISM
CLINICAL CORRELATES
THYROID HORMONE ACTION ON ENERGY METABOLISM
THYROID HORMONE ACTION ON RESTING ENERGY EXPENDITURE
THYROID HORMONE ACTION ON ADAPTIVE THERMOGENESIS
THYROID HORMONE ACTION ON ACTIVITY-RELATED ENERGY EXPENDITURE
THYROID HORMONE ACTION ON THERMIC EFFECT OF FOOD
ENERGY STATUS AND THYROID HORMONE HOMEOSTASIS
CLINICAL CORRELATES
POTENTIAL USE OF THYROID HORMONE AS TREATMENT FOR WEIGHT LOSS AND DYSLIPIDEMIA
CONCLUSIONS
ACKNOWLEDGMENTS
REFERENCES
Chapter 32: The skeletal system in thyrotoxicosis
REGULATION OF THYROID STATUS
CONTROL OF INTRACELLULAR T3 AVAILABILITY
MECHANISM OF THYROID HORMONE ACTION
ROLE OF TSH IN BONE
BONE REMODELING CYCLE
SKELETAL CONSEQUENCES OF CHILDHOOD THYROTOXICOSIS
SKELETAL EFFECTS OF THYROID HORMONES IN ADULTS
POPULATION STUDIES IN NORMAL EUTHYROID INDIVIDUALS
STUDIES OF ADULT THYROTOXICOSIS
EFFECTS OF TREATMENT FOR THYROTOXICOSIS
SUBCLINICAL HYPERTHYROIDISM
PATIENTS TREATED WITH SUPPRESSIVE DOSES OF THYROXINE
REFERENCES
Chapter 33: Thyroid dermopathy and thyroid acropachy
THYROID DERMOPATHY
HISTOLOGIC FINDINGS IN THYROID DERMOPATHY
CLINICAL MANIFESTATIONS
PATHOGENESIS
DIFFERENTIAL DIAGNOSIS
TREATMENT
OUTCOMES OF THERAPY OF THYROID DERMOPATHY
FUTURE DIRECTIONS FOR THERAPY
THYROID ACROPACHY
REFERENCES
Chapter 34: Psychiatric and cognitive effects of thyrotoxicosis
INTRODUCTION
NEUROPSYCHIATRIC MANIFESTATIONS OF OVERT THYROTOXICOSIS
COGNITIVE MANIFESTATIONS OF OVERT THYROTOXICOSIS
SUBCLINICAL THYROTOXICOSIS: NEUROPSYCHIATRIC AND COGNITIVE ASPECTS
DIFFERENTIAL DIAGNOSIS: BEHAVIORAL SYNDROMES THAT MAY MIMIC THYROTOXICOSIS
PSYCHOLOGICAL FACTORS IN THE PATHOPHYSIOLOGY OF THYROTOXICOSIS
TREATMENT OF THYROTOXICOSIS: NEUROPSYCHIATRIC ASPECTS
POSSIBLE LINK BETWEEN THYROID HORMONE AND ATTENTION DEFICIT/HYPERACTIVITY DISORDER
USE OF THYROID HORMONE IN AFFECTIVE DISORDERS
LITHIUM AND THYROID FUNCTION
REFERENCES
Chapter 35: Thyrotoxic storm
CLINICAL FEATURES
LABORATORY FINDINGS
PATHOGENESIS
TREATMENT
THERAPY TO REDUCE THYROID HORMONE SYNTHESIS AND SECRETION
THERAPY DIRECTED AGAINST SYSTEMIC DISTURBANCES
THERAPY DIRECTED AGAINST THE PERIPHERAL ACTIONS OF THYROID HORMONE
THERAPY DIRECTED AGAINST PRECIPITATING ILLNESS
REFERENCES
C. Diagnosis and Management of Thyrotoxicosis
Chapter 36: Diagnosis of thyrotoxicosis
INTRODUCTION
CLINICAL DIAGNOSIS
CLUES FROM ROUTINE LABORATORY TESTS
LABORATORY TESTING FOR THYROTOXICOSIS
SERUM THYROXINE DETERMINATIONS
SERUM TRIIODOTHYRONINE DETERMINATIONS
SERUM THYROTROPIN DETERMINATIONS
SCREENING, CASE FINDING, AND DIAGNOSIS
DIAGNOSING THE CAUSE OF THYROTOXICOSIS
REFERENCES
Chapter 37: Treatment of thyrotoxicosis
INTRODUCTION
THYROTOXICOSIS CAUSED BY GRAVES DISEASE
DRUG THERAPY OF THYROTOXICOSIS CAUSED BY GRAVES DISEASE
ANTITHYROID DRUGS (Fig. 37-1)
MECHANISMS OF ACTION
INTRATHYROIDAL ACTIONS
EXTRATHYROIDAL ACTIONS
EFFECTS ON THE IMMUNE SYSTEM
CLINICAL PHARMACOLOGY OF THE ANTITHYROID DRUGS
METHIMAZOLE
PROPYLTHIOURACIL
CLINICAL CONSIDERATIONS IN THE USE OF ANTITHYROID DRUGS
SIDE EFFECTS OF ANTITHYROID DRUGS
FOLLOW-UP OF PATIENTS TAKING AN ANTITHYROID DRUG FOR GRAVES DISEASE
REMISSIONS AND ANTITHYROID DRUG THERAPY
THERAPY FACTORS RELATING TO REMISSION OF GRAVES DISEASE
DISCONTINUATION OF ANTITHYROID DRUG THERAPY
OTHER DRUGS USED IN THE TREATMENT OF THYROTOXICOSIS CAUSED BY GRAVES DISEASE
INORGANIC IODIDE
ORAL CHOLECYSTOGRAPHIC AGENTS
β-ADRENERGIC ANTAGONIST DRUGS
RADIOACTIVE IODINE THERAPY FOR THYROTOXICOSIS (Fig. 37-1)
PRACTICAL THERAPEUTIC CONSIDERATIONS
COMPLICATIONS AND POTENTIAL RISKS OF RADIOIODINE THERAPY
POSTRADIOIODINE WORSENING OF THYROID FUNCTION
RADIOIODINE THERAPY AND GRAVES OPHTHALMOPATHY
INDICATIONS FOR RADIOIODINE THERAPY
SURGICAL THERAPY FOR THYROTOXICOSIS (Fig. 37-1)
SPECIAL CONSIDERATIONS IN THE TREATMENT OF THYROTOXICOSIS
TREATMENT OF CHILDREN AND ADOLESCENTS
TREATMENT OF ELDERLY PATIENTS
THYROTOXICOSIS IN PREGNANT WOMEN AND DURING LACTATION
THYROTOXIC STORM
THYROTOXICOSIS DUE TO TOXIC ADENOMA AND MULTINODULAR GOITER
TOXIC ADENOMA
TOXIC MULTINODULAR GOITER
REFERENCES
Chapter 38: Subclinical thyrotoxicosis
ETIOLOGY
ENDOGENOUS SUBCLINICAL THYROTOXICOSIS
EXOGENOUS SUBCLINICAL THYROTOXICOSIS
EVALUATION
DIFFERENTIAL DIAGNOSIS
EPIDEMIOLOGY AND NATURAL HISTORY
CLINICAL AND BIOLOGIC IMPORTANCE
PHYSIOLOGY OF SUPPRESSION OF TSH SECRETION
CARDIOVASCULAR CONSEQUENCES
BONE AND MINERAL METABOLISM
COGNITIVE DYSFUNCTION AND DEMENTIA
TREATMENT
CHOICE OF TREATMENT MODALITY
SIDE EFFECTS OF TREATMENT FOR SUBCLINICAL THYROTOXICOSIS
FUTURE DIRECTIONS
REFERENCES
Section IV: Thyroid Diseases: Hypothyroidism
A. Causes of Hypothyroidism
Chapter 39: Chronic autoimmune thyroiditis
INTRODUCTION
PREDISPOSITION TO CHRONIC AUTOIMMUNE THYROIDITIS
PATHOGENESIS OF CHRONIC AUTOIMMUNE THYROIDITIS
ANTIGEN PRESENTATION
T-CELL RESPONSES
B-CELL RESPONSES
EFFECTOR MECHANISMS
EXPERIMENTAL AUTOIMMUNE THYROIDITIS
CLINICAL ASPECTS
ASSOCIATED DISORDERS
REFERENCES
Chapter 40: Genetic defects causing hypothyroidism
MONOGENIC CAUSES OF THYROID DYSGENESIS
KEY TRANSCRIPTION FACTOR MUTATIONS IN TD
NKX2-1
PAX8
FOXE1
GLIS3
TSHR
ADDITIONAL GENES ASSOCIATED WITH TD
NKX2-5
JAG1
CDCA8 (BOREALIN)
TUBB1
NETRIN 1 (NTN1)
SYNDROMES WHICH MAY BE ASSOCIATED WITH CH
GENETIC CAUSES OF DYSHORMONOGENESIS
THYROGLOBULIN
TPO
DUOX2 AND DUOXA2
IYD (PREVIOUSLY KNOWN AS DEHAL1)
SLC5A5 (NIS)
SLC26A4 (PENDRIN)
SLC26A7
EVIDENCE FOR AN UNDIAGNOSED GENETIC COMPONENT IN TD
REFERENCES
Chapter 41: Primary hypothyroidism due to other causes
INTRODUCTION
RADIOACTIVE IODINE (131I THERAPY)
THYROIDECTOMY
TREATMENT OF TOXIC NODULAR GOITER
TREATMENT OF NONTOXIC NODULAR GOITER
EXTERNAL RADIATION
HYPOTHYROIDISM DUE TO THERAPEUTIC PHARMACOLOGIC AGENTS
LITHIUM CARBONATE
CYTOKINES
AMIODARONE
TYROSINE KINASE INHIBITORS
IMMUNE CHECKPOINT INHIBITORS
OTHER DRUGS
HYPOTHYROIDISM DUE TO INFILTRATIVE DISORDERS
RIEDEL THYROIDITIS (INVASIVE FIBROUS THYROIDITIS)
AMYLOIDOSIS
SARCOIDOSIS
SCLERODERMA
HEMOCHROMATOSIS
CYSTINOSIS
OTHER INFILTRATIVE OR INFECTIOUS DISORDERS (SEE CHAPTER 22)
PRIMARY THYROID LYMPHOMA
CONSUMPTIVE HYPOTHYROIDISM
INDUSTRIAL AND ENVIRONMENTAL AGENTS (SEE CHAPTER 12)
EMBRYOLOGIC VARIANTS
LINGUAL THYROID (SEE CHAPTER 63)
REFERENCES
Chapter 42: Central hypothyroidism
INTRODUCTION
EPIDEMIOLOGY
PATHOGENESIS
CLINICAL FEATURES AND DIAGNOSIS
TREATMENT OF CeH
REFERENCES
B. Organ System Manifestations of Hypothyroidism
Chapter 43: Overview of the clinical manifestations of hypothyroidism
INTRODUCTION
CLINICAL MANIFESTATIONS
OVERT HYPOTHYROIDISM
SUBCLINICAL HYPOTHYROIDISM
CARDIOVASCULAR DISEASE AND MORTALITY
PULMONARY SYSTEM
NEUROPSYCHIATRIC FEATURES
MUSCULOSKELETAL SYSTEM
INFECTIOUS COMPLICATIONS
SKIN AND CONNECTIVE TISSUE
KIDNEYS AND ELECTROLYTE METABOLISM
GASTROINTESTINAL TRACT AND LIVER
HEMATOLOGY AND HEMOSTASIS
PITUITARY DISORDERS IN HYPOTHYROIDISM
ADRENAL DISORDERS IN HYPOTHYROIDISM
SUMMARY
REFERENCES
Chapter 44: Hypothyroidism and the heart
CLINICAL CONSEQUENCES OF HYPOTHYROIDISM
CV SYMPTOMS AND SIGNS
ELECTROCARDIOGRAPHIC CHANGES IN HYPOTHYROIDISM
CORONARY ARTERY DISEASE IN HYPOTHYROIDISM
CV RISK FACTORS IN HYPOTHYROIDISM
LIPIDS
BLOOD PRESSURE AND VASCULAR DYSFUNCTION
THROMBOGENESIS
SUBCLINICAL HYPOTHYROIDISM
SPECIAL SITUATIONS IN HYPOTHYROIDISM RELATED TO THE HEART
POSTACUTE MYOCARDIAL INFARCTION
HEART FAILURE
TREATMENT OF HYPOTHYROIDISM IN PATIENTS WITH CORONARY ARTERY DISEASE
CARDIAC SURGERY AND CARDIAC TRANSPLANTATION PROCEDURES
REFERENCES
Chapter 45: The skeletal system in hypothyroidism
PHYSIOLOGIC CONTROL OF THYROID HORMONE ACTION
THYROID HORMONE TRANSPORT AND METABOLISM IN BONE
THYROID HORMONE RECEPTOR FUNCTION IN BONE
ROLE OF TSH ON SKELETAL GROWTH AND MATURATION
SKELETAL DEVELOPMENT
SKELETAL CONSEQUENCES OF CHILDHOOD HYPOTHYROIDISM
SKELETAL CONSEQUENCES OF IMPAIRED SENSITIVITY TO THYROID HORMONE
SKELETAL CONSEQUENCES OF ADULT HYPOTHYROIDISM
A POSSIBLE ROLE FOR THYROID HORMONE SIGNALING IN OSTEOARTHRITIS
REFERENCES
Chapter 46: Psychiatric and cognitive effects of hypothyroidism
INTRODUCTION
PSYCHIATRIC AND COGNITIVE EFFECTS OF OVERT HYPOTHYROIDISM
PSYCHIATRIC AND COGNITIVE EFFECTS OF SUBCLINICAL HYPOTHYROIDISM
EFFECT OF THYROID FUNCTION VARIATIONS WITHIN THE NORMAL RANGE ON MOOD AND COGNITION
HASHIMOTO ENCEPHALOPATHY
REFERENCES
Chapter 47: Myxedema Coma
INTRODUCTION
CLINICAL FEATURES: PRECIPITATING EVENTS
GENERAL DESCRIPTION
HYPOTHERMIA
RESPIRATORY SYSTEM
CARDIOVASCULAR MANIFESTATIONS
GASTROINTESTINAL MANIFESTATIONS
RENAL AND ELECTROLYTE MANIFESTATIONS
NEUROPSYCHIATRIC MANIFESTATIONS
INFECTIONS
DIAGNOSIS
TREATMENT
VENTILATORY SUPPORT
HYPONATREMIA
HYPOTHERMIA
HYPOTENSION
GLUCOCORTICOID THERAPY
THYROID HORMONE THERAPY
COMMENTS
REFERENCES
C. Management of Hypothyroidism
Chapter 48: Diagnosis of hypothyroidism
INTRODUCTION
CLINICAL DIAGNOSIS
CLINICAL MANIFESTATIONS
PREDISPOSITION TO HYPOTHYROIDISM
CHRONIC AUTOIMMUNE THYROIDITIS AND HYPOTHYROIDISM
LABORATORY TESTING
SERUM THYROXINE DETERMINATIONS
SERUM TSH DETERMINATIONS
OTHER MEASURES OF THYROID HORMONE ACTION
SCREENING, CASE FINDING, AND DIAGNOSIS
DIAGNOSING THE CAUSE OF HYPOTHYROIDISM
FUTURE ADVANCES IN LABORATORY ASSESSMENT
REFERENCES
Chapter 49: Treatment of hypothyroidism
HISTORICAL PERSPECTIVE ON THE TREATMENT OF HYPOTHYROIDISM
LEVOTHYROXINE THERAPY
ENDPOINTS DURING LEVOTHYROXINE THERAPY
FACTORS AFFECTING LEVOTHYROXINE DOSE
INITIATION AND ADJUSTMENT OF LEVOTHYROXINE THERAPY
CHOICE OF LEVOTHYROXINE PRODUCT
LEVOTHYROXINE ABSORPTION, METABOLISM, AND TRANSPORT
LEVOTHYROXINE THERAPY IN SPECIFIC SUBPOPULATIONS
PATIENT SATISFACTION WITH LEVOTHYROXINE THERAPY
LEVOTHYROXINE THERAPY AND T3 LEVELS
THERAPIES OTHER THAN LEVOTHYROXINE
THYROID EXTRACTS
SYNTHETIC COMBINATION THERAPY
LIOTHYRONINE THERAPY
SUMMARY
REFERENCES
Chapter 50: Subclinical hypothyroidism
INTRODUCTION
ETIOLOGY AND NATURAL HISTORY
CLINICAL AND BIOLOGIC IMPORTANCE
CURRENT EVIDENCE
TREATMENT CONSIDERATIONS
TREATMENT RECOMMENDATIONS
CONCLUSIONS
REFERENCES
Section V: Thyroid Diseases: Nontoxic Diffuse and Multinodular Goiter
Chapter 51: Multinodular goiter: pathogenesis and management
INTRODUCTION
ETIOLOGY
EPIDEMIOLOGY
NATURAL HISTORY
CLINICAL MANIFESTATIONS
DIAGNOSIS EVALUATION
MANAGEMENT
IODINE SUPPLEMENTATION
TSH SUPPRESSIVE THERAPY WITH LEVOTHYROXINE
ANTITHYROID DRUGS
SURGERY
131I THERAPY
OTHER TREATMENT OPTIONS
SUMMARY
REFERENCES
Chapter 52: Clinical evaluation and management of thyroid nodules
CLINICAL EVALUATION
LABORATORY EVALUATION
SERUM HORMONE AND OTHER MEASUREMENTS
IMAGING STUDIES
ULTRASONOGRAPHY
ELASTOGRAPHY
RADIONUCLIDE THYROID SCINTIGRAPHY
OTHER IMAGING STUDIES
FINE-NEEDLE ASPIRATION BIOPSY
RISK STRATIFICATION FOR THYROID NODULES
TECHNIQUE OF FINE-NEEDLE BIOPSY
RESULTS OF FINE-NEEDLE BIOPSY
LIMITATIONS OF FINE-NEEDLE ASPIRATION BIOPSY OF THYROID NODULES
CLINICAL RECOMMENDATIONS BASED UPON FNA CYTOLOGY RESULTS
NONDIAGNOSTIC CYTOLOGY: BETHESDA I
BENIGN CYTOLOGY: BETHESDA II
ATYPIA OF UNDETERMINED SIGNIFICANCE/FOLLICULAR LESION OF UNDERMINED SIGNIFICANCE (AUS/FLUS) CYTOLOGY: BETHESDA III
FOLLICULAR NEOPLASM CYTOLOGY (INCLUDES HüRTHLE CELL NEOPLASM): BETHESDA IV
ROLE OF MOLECULAR TESTING FOR BETHESDA III AND IV NODULES
SUSPICIOUS FOR MALIGNANCY CYTOLOGY: BETHESDA V
MALIGNANT CYTOLOGY: BETHESDA VI
TREATMENT AFTER THYROID SURGERY
REFERENCES
Section VI: Thyroid Cancers
Chapter 53: Carcinomas of follicular epithelium: epidemiology and pathogenesis
RADIATION
EXTERNAL RADIATION AND THYROID CARCINOMA
INTERNAL RADIATION AND THYROID CARCINOMA
COMPARISON OF EXTERNAL AND INTERNAL RADIATION
PREVENTING IODINE 131–RELATED THYROID CARCINOMA
EVALUATION OF IRRADIATED PATIENTS
RADIATION AND OTHER HEAD AND NECK TUMORS
CLINICAL FEATURES OF RADIATION-RELATED THYROID NEOPLASMS
GENETIC PREDISPOSITION
SYNDROMIC NONMEDULLARY THYROID CARCINOMA
NONSYNDROMIC FAMILIAL NONMEDULLARY THYROID CARCINOMA (FNMTC)
GENETIC SUSCEPTIBILITY
PRE-EXISTING THYROID DISEASE
HORMONAL AND REPRODUCTIVE FACTORS
DIETARY FACTORS
IODINE AND GOITROGENS
OTHER DIETARY FACTORS
ANTHROPOMORPHIC AND METABOLIC FACTORS
SMOKING AND OTHER ENVIRONMENTAL AGENTS
SUMMARY
REFERENCES
Chapter 54: Genomic landscapes of thyroid cancers of follicular cell derivation
GENOMIC HALLMARKS OF NEOPLASMS ARISING FROM THYROID FOLLICULAR CELLS
FOLLICULAR NEOPLASMS
AUTONOMOUSLY FUNCTIONING ADENOMA
FOLLICULAR ADENOMA AND CARCINOMA
PAPILLARY CARCINOMA
NIFTP
RARE PTC VARIANTS
OTHER SOMATIC MUTATIONS
TERT PROMOTER MUTATIONS
SOMATIC COPY NUMBER ALTERATIONS
HÜRTHLE CELL NEOPLASMS
POORLY DIFFERENTIATED THYROID CANCER
ANAPLASTIC THYROID CANCER
GENETIC SUSCEPTIBILITY AND ENVIRONMENTAL FACTORS
DIAGNOSTIC IMPLICATIONS OF THYROID CANCER GENOMICS
REFERENCES
Chapter 55: Carcinoma of the follicular epithelium: surgical therapy
INTRODUCTION
THYROIDECTOMY NOMENCLATURE
EXTENT OF THYROIDECTOMY AND RISK OF COMPLICATIONS
SURGERY FOR INDETERMINATE THYROID NODULES
THYROIDECTOMY FOR THYROID CARCINOMA DERIVED FROM FOLLICULAR EPITHELIUM
CERVICAL LYMPH NODE DISSECTION NOMENCLATURE
EXTENT OF LYMPH NODE DISSECTION AND RISK OF COMPLICATIONS
LYMPHATIC DRAINAGE AND LOCATION OF NODAL METASTASIS IN THYROID CARCINOMA DERIVED FROM FOLLICULAR EPITHELIUM
CLINICAL ASPECTS OF NODAL METASTASIS IN THYROID CARCINOMA DERIVED FROM FOLLICULAR EPITHELIUM
PROGNOSIS OF NODAL METASTASIS IN THYROID CARCINOMA DERIVED FROM FOLLICULAR EPITHELIUM
CENTRAL LYMPH NODE DISSECTION
LATERAL LYMPH NODE DISSECTION
SUMMARY
REFERENCES
Chapter 56: Staging and prognosis of differentiated thyroid cancer
INTRODUCTION
STAGING TO PREDICT RISK OF THYROID CANCER DEATH
ELEMENTS AND COMPARISON OF PUBLISHED STAGING SYSTEMS
EVOLUTION OF THE TNM SYSTEM TO THE CURRENT 8TH EDITION
VALIDATION AND CONTROVERSIES IN 8TH EDITION TNM STAGING
PREDICTING THE RISK OF THYROID CANCER RECURRENCE
ELEMENTS OF INITIAL RISK STRATIFICATION SYSTEMS
VALIDATION AND CONTROVERSIES FOR INITIAL RISK SYSTEMS
DYNAMIC RISK STRATIFICATION/RESPONSE-TO-THERAPY
ELEMENTS OF DYNAMIC RISK STRATIFICATION
VALIDATION AND CONTROVERSIES FOR DYNAMIC RISK STRATIFICATION
HOW TO USE CURRENT RISK STRATIFICATION SYSTEMS IN PRACTICE
CONCLUSIONS
REFERENCES
Chapter 57: Medical management of differentiated epithelial cell thyroid cancer
RADIOACTIVE IODINE THERAPY
THE GOALS OF THE FIRST ADMINISTERED ACTIVITY OF RADIOACTIVE IODINE AFTER THYROIDECTOMY
ABLATION OF RESIDUAL NORMAL THYROID TISSUE
RAI TREATMENT AS AN ADJUVANT THERAPY
PREPARATION FOR RAI THERAPY
SELECTION OF RADIOACTIVE IODINE ACTIVITY FOR REMNANT ABLATION
WHOLE-BODY 131I SCANS AND SPECT/CT
RAI THERAPY FOR LOCAL OR DISTANT METASTATIC DISEASE
INDICATIONS FOR RAI THERAPY
TREATMENT OF PATIENTS WITH HIGH SERUM THYROGLOBULIN LEVELS AND NEGATIVE IMAGING STUDIES
COMPLICATIONS OF RAI THERAPY
FOLLOW-UP PARADIGMS
EARLY FOLLOW-UP RECOMMENDATIONS (FIRST YEAR AFTER INITIAL THERAPY)
FOLLOW-UP PARADIGMS BASED ON RESPONSE TO THERAPY RESTRATIFICATION
ONGOING, DYNAMIC RISK ASSESSMENT DURING LONG-TERM FOLLOW-UP
TSH-SUPPRESSIVE THYROID HORMONE THERAPY
EXTERNAL BEAM RADIOTHERAPY
SYSTEMIC THERAPY FOR ADVANCED DISEASE
BIOLOGICALLY TARGETED THERAPIES
CYTOTOXIC CHEMOTHERAPY
OTHER PALLIATIVE INTERVENTIONS FOR SYMPTOMATIC METASTATIC DTC
REFERENCES
Chapter 58: Papillary microcarcinomas
INCREASING INCIDENCE OF THYROID CANCER WITH STABLE MORTALITY
SURGERY OF PAPILLARY MICROCARCINOMA AND OUTCOMES
FREQUENT MULTIPLICITY AND REGIONAL LYMPH NODE METASTASIS
PROGNOSIS OF HIGH-RISK AND LOW-RISK PAPILLARY MICROCARCINOMA
SURGICAL APPROACH TO PMCs
ACTIVE SURVEILLANCE OF LOW-RISK PAPILLARY MICROCARCINOMA
HISTORY AND HYPOTHESIS
PROTOCOL OF THE ACTIVE SURVEILLANCE AT KUMA HOSPITAL
OUTCOMES OF ACTIVE SURVEILLANCE
EVALUATION OF THE RISK OF TRACHEA AND RECURRENT LARYNGEAL NERVE INVASION
INCIDENCES OF UNFAVORABLE EVENTS IN IMMEDIATE SURGERY VERSUS ACTIVE SURVEILLANCE
MEDICAL ECONOMY OF MANAGEMENT OF PAPILLARY MICROCARCINOMA
FACTORS THAT MIGHT BE ASSOCIATED WITH DISEASE PROGRESSION
NATURAL HISTORY OF PAPILLARY CARCINOMA
LIFETIME PROBABILITY OF DISEASE PROGRESSION
TUMOR VOLUME KINETICS DURING ACTIVE SURVEILLANCE
ESTIMATING TUMOR GROWTH BEFORE PRESENTATION
IMPLEMENTING ACTIVE SURVEILLANCE
REFERENCES
Chapter 59: Medullary thyroid cancer
NATURAL HISTORY
TUMOR PROGRESSION
PREOPERATIVE SCREENING
SURGICAL TREATMENT
DYNAMIC RISK STRATIFICATION AND FOLLOW-UP
RECURRENT AND PERSISTENT DISEASE
REOPERATION
DISTANT DISEASE
CONCLUSION
REFERENCES
Chapter 60: Poorly differentiated thyroid cancer, anaplastic thyroid cancer, and miscellaneous tumors of the thyroid
POORLY DIFFERENTIATED THYROID CANCER
DEFINITION/EPIDEMIOLOGY
TREATMENT/PROGNOSIS
ANAPLASTIC THYROID CANCER
INTRODUCTION
EPIDEMIOLOGY
PATHOGENESIS
CLINICAL PRESENTATION AND DIFFERENTIAL DIAGNOSIS
PATHOLOGY
GENOMICS/MOLECULAR PATHOLOGY/IMMUNOLOGY
STAGING
MANAGEMENT—GENERAL CONSIDERATIONS
MANAGEMENT—STAGE IVA
MANAGEMENT—STAGE IVB
MANAGEMENT—STAGE IVC
MANAGEMENT—OLIGOMETASTATIC STAGE IVC
PALLIATIVE AND HOSPICE CARE
ATC SUMMARY
MISCELLANEOUS TUMORS OF THE THYROID GLAND
HYALINIZING TRABECULAR TUMOR
SQUAMOUS CELL CARCINOMA
THYROID MUCOEPIDERMOID CARCINOMA
SCLEROSING MUCOEPIDERMOID CARCINOMA WITH EOSINOPHILIA
MUCINOUS CARCINOMA OF THE THYROID
ECTOPIC THYMOMA
SPINDLE EPITHELIAL TUMOR WITH THYMUS-LIKE DIFFERENTIATION
INTRATHYROID THYMIC CARCINOMA
PARAGANGLIOMA AND MESENCHYMAL/STROMAL TUMORS
HEMATOLYMPHOID TUMORS
GERM CELL TUMORS (BENIGN TERATOMA, IMMATURE TERATOMA, MALIGNANT TERATOMA)
SECONDARY MALIGNANCIES OF THE THYROID
ACKNOWLEDGMENTS
REFERENCES
Chapter 61: Thyroid cancer in children
RISK OF THYROID CANCER IN THE PEDIATRIC PATIENT WITH A THYROID NODULE
DIFFERENTIATED THYROID CANCERS
PAPILLARY THYROID CARCINOMA (PTC)
PAPILLARY THYROID MICROCARCINOMA (PTMC)
FOLLICULAR VARIANT PTC
FOLLICULAR THYROID CARCINOMA (FTC)
MEDULLARY THYROID CARCINOMA
MULTIPLE ENDOCRINE NEOPLASIA 2A
MULTIPLE ENDOCRINE NEOPLASIA 2B
EARLY THYROIDECTOMY IN MEN2
MANAGEMENT OF MTC IN MEN2
REFERENCES
Section VII: The Thyroid in Infancy and Childhood
Chapter 62: The maturation of thyroid function in the fetus, in the perinatal period and during childhood
MATURATION OF THYROID FUNCTION IN UTERO
ORGANOGENESIS AND STRUCTURAL DIFFERENTIATION OF THE THYROID GLAND
FUNCTIONAL DIFFERENTIATION OF THE THYROID GLAND AND ONSET OF THYROID HORMONE SYNTHESIS
THE ROLE OF THE PLACENTA FOR MATERNOFETAL INTERACTION
MATURATION OF THE HYPOTHALAMIC–PITUITARY–THYROID AXIS
SYNTHESIS OF THE THYROID HORMONE TRANSPORT PROTEINS
REGULATION OF THYROID HORMONE LEVELS IN UTERO BY SULFATION
REGULATION OF THYROID HORMONE LEVELS IN UTERO BY DEIODINATION
ONTOGENY OF TRANSMEMBRANE THYROID HORMONE TRANSPORTERS
ONTOGENY OF THYROID HORMONE RECEPTORS
THE ROLE OF THYROID HORMONES FOR THE FETUS AND THE CHILD
BRAIN DEVELOPMENT
COCHLEA DEVELOPMENT
RETINA DEVELOPMENT
MUSCLE AND MYOCARDIAL DEVELOPMENT
BONE DEVELOPMENT AND LINEAR GROWTH
METABOLIC EFFECTS
PERINATAL AND POSTNATAL CHANGES IN THYROID HORMONE SYNTHESIS AND METABOLISM
PHYSIOLOGIC CHANGES IN THE TERM NEONATE
THYROID FUNCTION IN THE PRETERM NEONATE
THYROID FUNCTION IN SMALL FOR GESTATIONAL AGE NEONATES
INFANTS, CHILDREN, AND ADOLESCENTS
REFERENCES
Chapter 63: Hypothyroidism in infants and children
CONGENITAL HYPOTHYROIDISM
NEWBORN SCREENING
RATIONALE FOR BIOCHEMICAL SCREENING FOR CH
PREMATURE AND VERY LOW–BIRTH-WEIGHT NEWBORNS
NEWBORNS WITH TRISOMY 21
EVALUATION OF NEWBORNS WITH A POSITIVE SCREENING RESULT
QUALITY ASSESSMENT OF SCREENING PROGRAMS
CLASSIFICATION OF CH (Table 63-2)
ETIOLOGY AND PATHOGENESIS
PERMANENT CH
TRANSIENT CH
CLINICAL PRESENTATION
DIAGNOSTIC EVALUATION (Table 63-3)
TREATMENT AND OUTCOME
ACQUIRED HYPOTHYROIDISM (CH)
ETIOLOGIES (Table 63-4)
CLINICAL PRESENTATION (Fig. 63-4)
EVALUATION
TREATMENT
PROGNOSIS
REFERENCES
Chapter 64: Impaired sensitivity to thyroid hormone: defects of transport, metabolism, and action
TH SECRETION, CELL-MEMBRANE TRANSPORT, METABOLISM, AND ACTION
THE PARADOX OF COEXISTING MANIFESTATIONS OF THYROID HORMONE DEFICIENCY AND EXCESS
THYROID HORMONE ACTION DEFECTS KNOWN AS RESISTANCE TO THYROID HORMONE
RESISTANCE TO THYROID HORMONE BETA (RTHβ)
CLINICAL CLASSIFICATION
INCIDENCE AND INHERITANCE
ETIOLOGY AND GENETICS
MOLECULAR MECHANISMS OF TR ACTION
PROPERTIES OF MUTANT TRβ RECEPTORS AND ASSOCIATED DOMINANT-NEGATIVE EFFECT
MOLECULAR BASIS OF THE VARIABLE RTHβ PHENOTYPE
RTHβ WITHOUT THRB GENE MUTATIONS (NON–TRβ-RTH)
ANIMAL MODELS OF RTHβ
PATHOGENESIS
PATHOLOGY
CLINICAL FEATURES
COURSE OF THE DISEASE
LABORATORY FINDINGS
TH AND ITS METABOLITES
THYROTROPIN AND OTHER THYROID STIMULATORS
THYROID GLAND ACTIVITY AND INTEGRITY OF HORMONE SYNTHESIS
IN VIVO EFFECTS OF TH
IN VITRO TESTS OF THYROID HORMONE ACTION
RESPONSES TO THE ADMINISTRATION OF THYROID HORMONE
EFFECTS OF OTHER DRUGS
DIFFERENTIAL DIAGNOSIS
TREATMENT
RESISTANCE TO THYROID HORMONE ALPHA (RTHα)
BACKGROUND
INCIDENCE AND INHERITANCE
ETIOLOGY AND GENETICS
MOLECULAR BASIS OF THE DEFECT AND PROPERTIES OF THE MUTANT TRα
ANIMAL MODELS OF RTHα (SEE ALSO ANIMAL MODELS UNDER RTHβ, ABOVE)
CLINICAL FEATURES
LABORATORY FINDINGS
DIFFERENTIAL DIAGNOSIS
TREATMENT
THYROID HORMONE CELL MEMBRANE TRANSPORTER DEFECT (THCMTD)
CELL MEMBRANE TRANSPORTERS OF TH
INHERITANCE AND INCIDENCE
ETIOLOGY
THE MCT8 GENE AND MUTATIONS
CLINICAL FEATURES AND COURSE OF THE DISEASE
LABORATORY FINDINGS
SERUM TESTS OF THYROID FUNCTION
OTHER SERUM TESTS
X-RAYS AND IMAGING
TESTS IN TISSUES
GENETIC TESTING
ANIMAL MODELS OF MCT8 DEFICIENCY
MOLECULAR BASIS OF THE DISORDER
DIFFERENTIAL DIAGNOSIS
TREATMENT
THYROID HORMONE METABOLISM DEFECT
INTRACELLULAR METABOLISM OF TH
ETIOLOGY AND GENETICS
INCIDENCE AND INHERITANCE
THE SBP2 GENE AND MUTATIONS
CLINICAL FEATURES AND COURSE OF THE DISEASE
LABORATORY FINDINGS
MOLECULAR BASIS OF THE DISORDER
THMD CAUSED BY MUTATION IN THE TRU-TCA1-1 GENE
ANIMAL MODELS OF THMD
DIFFERENTIAL DIAGNOSIS
TREATMENT
ACKNOWLEDGMENTS
REFERENCES
Chapter 65: Hyperthyroidism in the neonate, child, and adolescent
CLINICAL EVALUATION OF THE HYPERTHYROID STATE
BIOCHEMICAL EVALUATION OF THYROID FUNCTION
GRAVES DISEASE
ANTITHYROID DRUG THERAPY
RADIOACTIVE IODINE THERAPY
THYROIDECTOMY AND RISKS
SOMATIC COMPLICATIONS OF GD
NEONATAL THYROTOXICOSIS
FETAL CONSIDERATIONS
OTHER CAUSES OF HYPERTHYROIDISM
HASHITOXICOSIS
SUMMARY
REFERENCES
Section VIII: Thyroid Disorders in Pregnancy and Postpartum
Chapter 66: Thyroid disorders during preconception, pregnancy, and the postpartum period
PRECONCEPTION
EPIDEMIOLOGY
PHYSIOLOGY
CLINICAL OUTCOMES AND MANAGEMENT
PREGNANCY
EPIDEMIOLOGY
PHYSIOLOGY
DIAGNOSIS OF THYROID DISEASE
OVERT HYPOTHYROIDISM
SUBCLINICAL HYPOTHYROIDISM
ISOLATED HYPOTHYROXINEMIA
AUTOIMMUNE THYROID DISEASE IN PREGNANCY
HYPERTHYROIDISM
POSTPARTUM
POSTPARTUM THYROIDITIS
REFERENCES
Index